In Vitro Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin

Abstract

We synthesized a novel water-soluble porphyrin THPP and its metalated derivative Zn-THPP having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S. Food and Drug Administration approved and clinically used sensitizer Photofrin, THPP showed ca. 2-3-fold higher in vitro photodynamic activity in different cell lines under identical conditions. The mechanism of the biological activity of these porphyrin systems has been evaluated through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, comet assay, poly(ADP-ribose)polymerase (PARP) cleavage, CM-H(2)DCFDA assay, DNA fragmentation, flow cytometric analysis, fluorescence, and confocal microscopy, which confirm the apoptotic cell death through predominantly reactive oxygen species (ROS). Moreover, THPP showed rapid cellular uptake and are localized in the nucleus of the cells as compared to Hoechst dye and Photofrin, thereby demonstrating its use as an efficient sensitizer in photodynamic therapy and live cell NIR nucleus imaging applications.

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

“…Moreover, THPP rapidly permeated into cells and localized in the nucleus, demonstrating its potential application as a NIR probe for PDT as well as nucleus imaging. 38 …”

“…In comparison with Photofrin, these probes have stronger intense fluorescence emission and singlet oxygen generation efficiency, showing the potential for PDT. 38 …”

Physicochemical characterisation and antimicrobial phototoxicity of an anionic porphyrin in natural deep eutectic solvents

“…Porphyrins are aromatic heterocycles that have been investigated as PS in photodynamic therapy (PDT) of cancer and microbial infections [12][13][14][15][16][17][18][19]. It is well documented that cationic PS efficiently photoinactivate both Gram-positive and Gram-negative bacteria, whereas neutral PS and anionic PS are predominantly phototoxic only to Gram-positive bacteria [18][19][20][21][22][23][24][25].…”

Improved antibacterial phototoxicity of a neutral porphyrin in natural deep eutectic solvents

“…Porphyrins are aromatic heterocyclic compounds that are ubiquitous in nature, and have been widely investigated in photodynamic therapy of tumours and microbial infections [3][4][5][6][7][8][9][10]. In cancer treatment neutral and negatively charged porphyrins (e.g.…”